- Email: [email protected]
CYTARABINE IN PREGNANCY
259 tation of the physician with a scientific training oriented to the handling and use of drugs. It is essential for pharmacists to be able to communicate with physicians and for there to be an interchange of knowledge for the benefit of the patient. Leighton would presumably dismiss, as "paramedicals" not worth a second thought, the vast numbers of scientifically (and not medically) trained people working in the pharmaceutical industry who provide doctors with the drugs without which they would be powerless. All of these have been "exposed to the fascinations of basic medical disciplines" and contribute greatly to the progress of medicine by their collective work. The physician is at the end of a long chain of expertise and I suspect now that many feel threatened when they see pharmacists, highly trained and knowledgeable, exercising some influence (not power) in their last bastion, the hospital ward. As an anxsthetist Leighton will probably, understandably, have little contact with his pharmacists, but it is a pity that he is not prepared to admit that pharmacists have a role to play in patient care a little wider than the ooe he ascribes to them. An occasional look at the Journal of Pharmaceutical Sciences or the International Journal of Pharmaceutics would open his eyes to a world about which he obviously knows nothing.
Department School of Pharmaceutical Sciences, of Pharmaceutics,
University of Strathclyde, Glasgow G1 1XW
A. T. FLORENCE
SiR,—Dr Leighton refers
the modern pharmacist. Perhis patients with "time saving" and "cheap-to-the-taxpayer" remedies such as woodlice syrup, four thieves’ vinegar, and dog-dirt. Like Leighton’s ideas, such remedies were around two or three hundred years ago.
haps
he would
prefer
to
to treat
Area Drug Information Service, General Hospital, Northampton NN1 5BD
PAUL C. ROWBOTHAM
NOMENCLATURE OF INTERFERONS
SIR,-Clinicians should be spared the trauma of writing prescriptions in the style Hu IFN-ot (18K) (July 19, p. 159). Such a style runs counter to many of the rules that govern the approved names devised or selected by the British Pharmacopoeia Commission, the international nonproprietary names, and the U.S. adopted names (USAN). The introduction of therapeutic substances obtained by genetic manipulation and tissue and cell culture will pose several problems of nomenclature, of which a multiplicity of interferons and their unambiguous distinction is but one. For interferon a solution might be to adopt a stem "-feron" to which prefixes are added, in the manner of stems such as -azepam, -cillin or -profen. A further descriptor may be necessary. The definition of each interferon will be simplified by adoption of a systematic nomenclature such as that advocated by the expert group to which your July 19 note refers. It is to be hoped that promulgation of "interferon" as the USAN for the Parke-Davis material code CI-8841 will not impede the development and international acceptance of a flexible nomenclature that the W.H.O. expert committee will have to devise, in consultation with national authorities. Meanwhile an opportunity exists for comment by those who look forward expectantly to selecting and prescribing from a range of interferons. National Institute for Biological Standards and Control, London NW3 6RB
D. H. CALAM
CYTARABINE IN PREGNANCY
SIR,-Dr Wagner and colleagues (July 12, p. 98) report
congenital abnormalities in the offspring of a woman cytarabine (cytosine arabinoside) at the time of conception, and refer to only one other "reported case of the administration of cytarabine to a pregnant woman". In fact over twenty such cases have been reported,1,2 including three women who conceived whilst taking the drug,3,4 as in Wagner’s case, and two others who received cytarabine at 10-12 weeks of pregnancy.5,6 No congenital abnormalities were reported in any of the seventeen normal infants (three premature), five therapeutic abortions, and one stillbirth following pre-eclamptic toxxmia which resulted, although one fetus showed a chromosomal abnormality.’3
severe
treated with
Leukæmia Unit, Royal Marsden Hospital, Sutton, Surrey SM2 5PT
G. MORGENSTERN
SALT AND HYPERTENSION
SIR,-Dr Trowell’s criticism (July 12, p. 88) of Professor Swales’ statement that salt protects from mortality from diarrhceal disease is unjust. None of the primitive peoples whose diets are low in sodium enjoy a favourable mortality experience. On the contrary, they have a high mortality, notably from diarrhceal disease. There is considerable doubt as to the true minimum daily requirement for sodium. The figure of 10 mmol cited by Trowell is just half of the more commonly accepted figure. However, a precarious existence on a diet containing the bare minimum capable of maintaining electrolyte balance is like living on the edge of a precipice. Quite minor disturbances in gastrointestinal function can lead to hyponatraemia and to dehydration. Trowell’s statement that the body does not store sodium is not entirely true. There is no measurable difference between the blood sodium concentration of individuals in the sodium loaded and in sodium depleted state. It appears that it is the state of the sodium reserves which influences the secretion of aldosterone, and not the concentration in blood. Homoeostatic mechanisms are most effective near the middle of their range, where they have the capacity to respond equally to variations in either direction. Maintenance of the right electrolyte balance is essential to most of the body’s vital processes, and the renin-angiotensin-aldosterone system is the mechanism which regulates electrolytes, and incidentally causes the changes in blood pressure necessary to achieve this. A sodium intake which allows this mechanism scope in both directions would, therefore, be expected to be associated with lower mortality than a higher or lower level of consumption. That this is probably so is suggested by our finding7 that mortality both from hypertensive diseases and from all causes has been lower in a group of towns in Essex and in this area whose water supply contained more than 100 mg/1 Na, and is therefore incompatible with adherence to a low sodium diet. Scunthorpe Health District, Scunthorpe DN15 8DT
J. S. ROBERTSON
1. Manoharan A, Leyden MJ. Acute non-lymphocytic leukæmia in the third trimester of pregnancy. Aust NZ J Med 1979; 9: 71-74. 2. Tobias SS, Morgenstern G, Bloom HJG, Powles RL. Doxorubicin in pregnancy. Lancet 1980; i: 776. 3. Maurer LH, Forcier RJ, McIntyre OR, Benirschke K. Fetal group C trisomy after cytosine arabinoside and thioguanine. Ann Intern Med 1971; 75: 809-10. 4. Moreno H, Castleberry RP, McCann WP. Cytosine arabinoside and 6-thioguanine in the treatment of childhood acute myeloblastic leukæmia. Cancer 1977; 40: 988-1004. 5. Sears HF, Reid J. Granulocytic sarcoma. Cancer 1976; 37: 1808-13. 6. Newcomb M, Balducci L, Thigpen JT, Morrison FS. Acute leukaemia in pregnancy: Successful delivery after cytarabine and doxorubicin. JAMA
1978; 239: 2691-92. 1. USAN Council. List 203 new names.
JAMA 1980; 243: 787-88.
7. Robertson JS, Slattery IA, Parker V. Water tality. Commun Med 1979; 1: 295-300.
sodium, hypertension
mor-
Department School of Pharmaceutical Sciences, of Pharmaceutics,
University of Strathclyde, Glasgow G1 1XW
A. T. FLORENCE
SiR,—Dr Leighton refers
the modern pharmacist. Perhis patients with "time saving" and "cheap-to-the-taxpayer" remedies such as woodlice syrup, four thieves’ vinegar, and dog-dirt. Like Leighton’s ideas, such remedies were around two or three hundred years ago.
haps
he would
prefer
to
to treat
Area Drug Information Service, General Hospital, Northampton NN1 5BD
PAUL C. ROWBOTHAM
NOMENCLATURE OF INTERFERONS
SIR,-Clinicians should be spared the trauma of writing prescriptions in the style Hu IFN-ot (18K) (July 19, p. 159). Such a style runs counter to many of the rules that govern the approved names devised or selected by the British Pharmacopoeia Commission, the international nonproprietary names, and the U.S. adopted names (USAN). The introduction of therapeutic substances obtained by genetic manipulation and tissue and cell culture will pose several problems of nomenclature, of which a multiplicity of interferons and their unambiguous distinction is but one. For interferon a solution might be to adopt a stem "-feron" to which prefixes are added, in the manner of stems such as -azepam, -cillin or -profen. A further descriptor may be necessary. The definition of each interferon will be simplified by adoption of a systematic nomenclature such as that advocated by the expert group to which your July 19 note refers. It is to be hoped that promulgation of "interferon" as the USAN for the Parke-Davis material code CI-8841 will not impede the development and international acceptance of a flexible nomenclature that the W.H.O. expert committee will have to devise, in consultation with national authorities. Meanwhile an opportunity exists for comment by those who look forward expectantly to selecting and prescribing from a range of interferons. National Institute for Biological Standards and Control, London NW3 6RB
D. H. CALAM
CYTARABINE IN PREGNANCY
SIR,-Dr Wagner and colleagues (July 12, p. 98) report
congenital abnormalities in the offspring of a woman cytarabine (cytosine arabinoside) at the time of conception, and refer to only one other "reported case of the administration of cytarabine to a pregnant woman". In fact over twenty such cases have been reported,1,2 including three women who conceived whilst taking the drug,3,4 as in Wagner’s case, and two others who received cytarabine at 10-12 weeks of pregnancy.5,6 No congenital abnormalities were reported in any of the seventeen normal infants (three premature), five therapeutic abortions, and one stillbirth following pre-eclamptic toxxmia which resulted, although one fetus showed a chromosomal abnormality.’3
severe
treated with
Leukæmia Unit, Royal Marsden Hospital, Sutton, Surrey SM2 5PT
G. MORGENSTERN
SALT AND HYPERTENSION
SIR,-Dr Trowell’s criticism (July 12, p. 88) of Professor Swales’ statement that salt protects from mortality from diarrhceal disease is unjust. None of the primitive peoples whose diets are low in sodium enjoy a favourable mortality experience. On the contrary, they have a high mortality, notably from diarrhceal disease. There is considerable doubt as to the true minimum daily requirement for sodium. The figure of 10 mmol cited by Trowell is just half of the more commonly accepted figure. However, a precarious existence on a diet containing the bare minimum capable of maintaining electrolyte balance is like living on the edge of a precipice. Quite minor disturbances in gastrointestinal function can lead to hyponatraemia and to dehydration. Trowell’s statement that the body does not store sodium is not entirely true. There is no measurable difference between the blood sodium concentration of individuals in the sodium loaded and in sodium depleted state. It appears that it is the state of the sodium reserves which influences the secretion of aldosterone, and not the concentration in blood. Homoeostatic mechanisms are most effective near the middle of their range, where they have the capacity to respond equally to variations in either direction. Maintenance of the right electrolyte balance is essential to most of the body’s vital processes, and the renin-angiotensin-aldosterone system is the mechanism which regulates electrolytes, and incidentally causes the changes in blood pressure necessary to achieve this. A sodium intake which allows this mechanism scope in both directions would, therefore, be expected to be associated with lower mortality than a higher or lower level of consumption. That this is probably so is suggested by our finding7 that mortality both from hypertensive diseases and from all causes has been lower in a group of towns in Essex and in this area whose water supply contained more than 100 mg/1 Na, and is therefore incompatible with adherence to a low sodium diet. Scunthorpe Health District, Scunthorpe DN15 8DT
J. S. ROBERTSON
1. Manoharan A, Leyden MJ. Acute non-lymphocytic leukæmia in the third trimester of pregnancy. Aust NZ J Med 1979; 9: 71-74. 2. Tobias SS, Morgenstern G, Bloom HJG, Powles RL. Doxorubicin in pregnancy. Lancet 1980; i: 776. 3. Maurer LH, Forcier RJ, McIntyre OR, Benirschke K. Fetal group C trisomy after cytosine arabinoside and thioguanine. Ann Intern Med 1971; 75: 809-10. 4. Moreno H, Castleberry RP, McCann WP. Cytosine arabinoside and 6-thioguanine in the treatment of childhood acute myeloblastic leukæmia. Cancer 1977; 40: 988-1004. 5. Sears HF, Reid J. Granulocytic sarcoma. Cancer 1976; 37: 1808-13. 6. Newcomb M, Balducci L, Thigpen JT, Morrison FS. Acute leukaemia in pregnancy: Successful delivery after cytarabine and doxorubicin. JAMA
1978; 239: 2691-92. 1. USAN Council. List 203 new names.
JAMA 1980; 243: 787-88.
7. Robertson JS, Slattery IA, Parker V. Water tality. Commun Med 1979; 1: 295-300.
sodium, hypertension
mor-